Mitochondrial DNA methylation is associated with Mediterranean diet adherence in a population of older adults with overweight and obesity.

Oxidative Medicine and Cellular Longevity

Petracci

Młodzik-Czyżewska

et al. 2022

Mitochondrial DNA copy number (mtDNAcn) has been proposed for use as a surrogate biomarker of mitochondrial health, and evidence suggests that mtDNA might be methylated. Intermediates of the one-carbon cycle (1CC), which is duplicated in the cytoplasm and mitochondria, have a major role in modulating the impact of diet on the epigenome. Moreover, epigenetic pathways and the redox system are linked by the metabolism of glutathione (GSH). In a cohort of 101 normal-weight and 97 overweight/obese subjects, we evaluated mtDNAcn and methylation levels in both mitochondrial and nuclear areas to test the association of these marks with body weight, metabolic profile, and availability of 1CC intermediates associated with diet. Body composition was associated with 1CC intermediate availability. Reduced levels of GSH were measured in the overweight/obese group ( p = 1.3 ∗ 10 − 5 ). A high BMI was associated with lower LINE-1 ( p = 0.004 ) and nominally lower methylenetetrahydrofolate reductase (MTHFR) gene methylation ( p = 0.047 ). mtDNAcn was lower in overweight/obese subjects ( p = 0.004 ) and independently correlated with MTHFR methylation levels ( p = 0.005 ) but not to LINE-1 methylation levels ( p = 0.086 ). DNA methylation has been detected in the light strand but not in the heavy strand of the mtDNA. Although mtDNA methylation in the light strand did not differ between overweight/obese and normal-weight subjects, it was nominally correlated with homocysteine levels ( p = 0.035 ) and MTHFR methylation ( p = 0.033 ). This evidence suggests that increased body weight might perturb mitochondrial-nuclear homeostasis affecting the availability of nutrients acting as intermediates of the one-carbon cycle.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Oxidative Medicine and Cellular Longevity

Petracci

Młodzik-Czyżewska

et al. 2022

“…However, a certain responsiveness of the mitochondrial epigenome to external stimuli, including but not limited to dietary elements, has been postulated [65,67,120]. Remarkably, Corsi and colleagues recently demonstrated that mtDNA methylation can change accordingly to the adherence to the Mediterranean diet [250], corroborating the hypothesis of a potential role of nutrition in the modulation of mtDNA methylation.…”

Section: Antioxidants and Mitochondria: From The General Function To mentioning

confidence: 91%

Mitochondrial DNA and Neurodegeneration: Any Role for Dietary Antioxidants?

Gabbianelli

2020

Antioxidants

The maintenance of the mitochondrial function is essential in preventing and counteracting neurodegeneration. In particular, mitochondria of neuronal cells play a pivotal role in sustaining the high energetic metabolism of these cells and are especially prone to oxidative damage. Since overproduction of reactive oxygen species (ROS) is involved in the pathogenesis of neurodegeneration, dietary antioxidants have been suggested to counteract the detrimental effects of ROS and to preserve the mitochondrial function, thus slowing the progression and limiting the extent of neuronal cell loss in neurodegenerative disorders. In addition to their role in the redox-system homeostasis, mitochondria are unique organelles in that they contain their own genome (mtDNA), which acts at the interface between environmental exposures and the molecular triggers of neurodegeneration. Indeed, it has been demonstrated that mtDNA (including both genetics and, from recent evidence, epigenetics) might play relevant roles in modulating the risk for neurodegenerative disorders. This mini-review describes the link between the mitochondrial genome and cellular oxidative status, with a particular focus on neurodegeneration; moreover, it provides an overview on potential beneficial effects of antioxidants in preserving mitochondrial functions through the protection of mtDNA.

“…[18] Methylation has been measured throughout the mitochondrial genome, in CpG sites but also in CpH (non-CG) dinucleotides, [19,20] and differ among tissues and cell types. [21,22] Strand-specific methylation levels in the D-loop area of mtDNA have been found as well and reported to vary in response to environmental stimuli, [23][24][25] including diet, [26][27][28] even though a clear mechanistic role of this epigenetic modification has not been defined yet.…”

Section: Introductionmentioning

confidence: 99%

“…Only a few studies reporting on the impact of diet on mtDNAcn and methylation have been published to this date. [26][27][28] Therefore, this research aims to test whether diet, TMA, and TMAO are associated with levels of mitochondrial DNA copy number and methylation in a group of healthy subjects having extremely healthy or unhealthy dietary patterns.…”

Section: Introductionmentioning

confidence: 99%

Diet, Trimethylamine Metabolism, and Mitochondrial DNA: An Observational Study

Molecular Nutrition Food Res

Malinowska

Petracci

et al. 2022

Scope: Mitochondrial DNA copy number (mtDNAcn) and its methylation level in the D-loop area have been correlated with metabolic health and are suggested to vary in response to environmental stimuli, including diet. Circulating levels of trimethylamine-n-oxide (TMAO), which is an oxidative derivative of the trimethylamine (TMA) produced by the gut microbiome from dietary precursors, have been associated with chronic diseases and are suggested to have an impact on mitochondrial dynamics. This study is aimed to investigate the relationship between diet, TMA, TMAO, and mtDNAcn, as well as DNA methylation. Methods and results: Two hundred subjects with extreme (healthy and unhealthy) dietary patterns are recruited. Dietary records are collected to assess their nutrient intake and diets' quality (Healthy Eating Index). Blood levels of TMA and TMAO, circulating levels of TMA precursors and their dietary intakes are measured. MtDNAcn, nuclear DNA methylation long interspersed nuclear element 1 (LINE-1), and strand-specific D-loop methylation levels are assessed. There is no association between dietary patterns and mtDNAcn. The TMAO/TMA ratio is negatively correlated with d-loop methylation levels but positively with mtDNAcn. Conclusions: These findings suggest a potential association between TMA metabolism and mitochondrial dynamics (and mtDNA), indicating a new avenue for further research.